Methylsalicylate 2-O-D-lactoside, a novel salicylic acid analogueacts as an antiinflammatoryagent on microglia and astrocytes
LAN Xi, LIU Rui , SUN Lan, ZHANG Tian-tai , DU Guan-hua
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Beijing Key Laboratory of Drug Target and Screening Research, Institute of Materia Medica, Chinese Academyof Medical Sciences & Peking Union Medical College, Beijing [KG*2]100050, China
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History+
Received
Revised
Published
1900-01-01
1900-01-01
2011-09-23
Issue Date
2020-07-22
Abstract
OBJECTIVE Neuroinflammation has been known to play a critical role in the pathogenesis of alzheimer′s disease (AD). Activation of microglia and astrocytes is a characteristic of brain inflammation. Epidemiological studies have shown that longterm use of nonsteroidal antiinflammatory drugs (NSAIDs) delays the onset of AD and suppresses its progression. Methylsalicylate-2-O-β-D-lactoside (DL0309) is a new molecule chemically related to salicylic acid. The present study aimed to evaluate the antiinflammatory effects of DL0309. METHODS Cells were pretreated for 1 h with DL0309 at the concentration of 0.1, 1 and 10 μmol·L-1 respectively, and then stimulated by lipopolysaccharide (LPS, 0.5 μg·ml-1) for 24 h. Pro-inflammatory cytokines (IL-6, IL-1β and TNF-α) levels, NO production and COX1/2 expression were measured. After exposing to LPS (0.5μg·ml-1) for 10min or 45 min, the activation of NF-κB signal pathway was measured by western blotting. RESULTS Our studies showed that DL0309 significantly inhibited LPSinduced the release of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) and the expression of inflammatory related proteins (iNOS, COX-1, and COX-2) in microglia and astrocytes. At the concentration of 10 μmol·L-1, DL0309 prominently inhibited LPS-induced the activation of NF-κB in glia cells via blocking the phosphorylation of IKK, p65 and IκB degradation. CONCLUSION We have first demonstrated that DL0309 exerts antiinflammatory effects in glia cells by inhibiting different proinflammatory cytokines and iNOS/NO. Furthermore, it also regulates the NF-κB signaling pathway by blocking IKK, IκB and p65 activation. It also acts as a non-selective COX inhibitor in glia cells. These studies suggest that DL0309 may be effective in the treatment of neuroinflammatory disorders including AD.
LAN Xi;LIU Rui;SUN Lan;ZHANG Tian-tai;DU Guan-hua.
Methylsalicylate 2-O-D-lactoside, a novel salicylic acid analogueacts as an antiinflammatoryagent on microglia and astrocytes. Chinese Journal of Pharmacology and Toxicology. 2011, 25(增刊): 32-32
